Clinical Trials /

Pre-Surgical Trial of the Combination of Metformin and Atorvastatin in Newly Diagnosed Operable Breast Cancer

NCT01980823

Description:

The purpose of this study is to determine the effects of combining metformin and atorvastatin treatment in patients with newly diagnosed breast cancer during the interval between breast biopsy and surgery. This study is designed to assess whether tumor proliferation, as measured by the natural log expression of Ki-67 staining of breast tumor cells, is reduced following approximately 2 weeks of treatment with the combination of metformin plus atorvastatin in patients with newly diagnosed breast cancer.

Related Conditions:
  • Breast Carcinoma In Situ
  • Invasive Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

URL:

https://clinicaltrials.gov/show/NCT01980823

Trial Eligibility

Document

Title

  • Brief Title: Pre-Surgical Trial of the Combination of Metformin and Atorvastatin in Newly Diagnosed Operable Breast Cancer
  • Official Title: Pre-Surgical "Window of Opportunity" Trial of the Combination of Metformin and Atorvastatin in Newly Diagnosed Operable Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: AAAM2306
  • NCT ID: NCT01980823

Conditions

  • Breast Cancer
  • Breast Tumors
  • Cancer of Breast

Interventions

DrugSynonymsArms
MetforminGlucophageMetformin-Atorvastatin combination
AtorvastatinLipitorMetformin-Atorvastatin combination

Purpose

The purpose of this study is to determine the effects of combining metformin and atorvastatin treatment in patients with newly diagnosed breast cancer during the interval between breast biopsy and surgery. This study is designed to assess whether tumor proliferation, as measured by the natural log expression of Ki-67 staining of breast tumor cells, is reduced following approximately 2 weeks of treatment with the combination of metformin plus atorvastatin in patients with newly diagnosed breast cancer.

Detailed Description

      Breast cancer cells require energy homeostasis shifts with enhanced anabolism to enable rapid
      growth and continued proliferation. The main energy regulatory system in eukaryotes and
      breast cancer cells is the AMP-activated kinase (AMPK) pathway. AMPK is triggered by changes
      in the AMP/Adenosine triphosphate (ATP) ratio thus impacting energy reserves and
      requirements. AMPK pathway closely interacts with the phosphoinositide 3-kinase (PI3K)/Akt
      signaling pathway, affecting the downstream function of the master regulator mammalian target
      of rapamycin (mTOR). Activation of AMPK has been shown in vitro to result in inhibition of
      proliferation of various cancer cell lines.

      Utilizing a pre-surgical model, the investigator plans to conduct a pilot study of 40 women
      with newly diagnosed invasive breast cancer or ductal carcinoma in-situ (DCIS) who will
      receive oral metformin and atorvastatin daily in the interval between diagnostic breast
      biopsy and definitive breast surgery.

      The goal is to determine if dual combination treatment with metformin plus atorvastatin
      significantly impacts tumor-based markers, such as proliferation, and blood-based biomarkers.

Trial Arms

NameTypeDescriptionInterventions
Metformin-Atorvastatin combinationExperimentalPatients will receive metformin and atorvastatin for approximately 2 weeks prior to breast surgery.
  • Metformin
  • Atorvastatin

Eligibility Criteria

        Inclusion Criteria:

          -  Female subjects with histologically-confirmed operable invasive breast cancer or DCIS,
             who undergo core needle biopsy followed by surgical excision at least 2 weeks after
             enrollment

          -  ≥ 5 mm by imaging/pathology of core to ensure enough pre- and post-treatment tissue
             for analysis

          -  Age ≥ 21 years. Breast cancer is uncommon in patients less than this age.

          -  No prior chemotherapy, radiation therapy, or breast resection within 6 months of study
             entry

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1

          -  Signed informed consent

        Exclusion Criteria:

          -  Currently on medication for diabetes or hypercholesterolemia

          -  Treatment with other investigational drugs within 6 months of study entry

          -  Strong Cytochrome P450 3A4 (abbreviated CYP3A4) (e.g., clarithromycin, HIV protease
             inhibitors, and itraconazole), given potential interactions with atorvastatin

          -  Renal impairment with a creatinine > 1.4 mg/dl

          -  Hepatic impairment: Aspartate transaminase (AST)/(SGOT), Alanine
             Transaminase(ALT)/(SGPT) ≥ 2.5 x upper limit of normal range (ULN), OR Total bilirubin
             ≥ 1.5 x ULN (subjects with Gilbert's syndrome can have bilirubin of up to 1.5 x ULN),
             OR Alkaline phosphatase > 2.5 x ULN
Maximum Eligible Age:N/A
Minimum Eligible Age:21 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in tissue levels of the proliferation marker Ki-67
Time Frame:Baseline, 2 weeks after start of treatment
Safety Issue:
Description:Tumor proliferation, as measured by the natural log expression of Ki-67 staining of breast tumor cells.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Columbia University

Trial Keywords

  • Breast Cancer
  • Metformin
  • Atorvastatin
  • Ki-67

Last Updated

July 15, 2019